Summary of Work: The purpose is to establish the neurobiological substrate of developmental stuttering using genetic linkage techniques. The goal is to identify gene products which may be used of develop neuroimaging techniques, which themselves may be used to characterize the neurobiology of developmental stuttering. The first arm of this project involves genetic linkage analysis in large multiplex families with members from several generations who stutter. During the past year we have collaborated with Mark Leppert of the University of Utah, in studying a large multigenerational kindred with branches in Idaho, Utah and Maine. Blood samples have been collected in 63 members of this family. The family has agreed to participate in the phenotyping portion of the study, and on-site evaluation of individuals for phenotypic assignment is scheduled. Genotyping will begin in the fall. Eight other multiplex families have been identified. Members of several generations of one family have agreed to participate, blood samples have been obtained and on-site phenotyping has been scheduled. As a result of publicizing the study among speech-language pathologists specializing in fluency disorders, we have ascertained 20 additional kindreds and have contacted a member in each. Members of one family are being evaluated. The second arm of this project involves candidate gene analyses, evaluating the fequencies of DNA polymorphisms for which gene products represent neurotransmitter receptors or rate-limiting synthetic enzymes of central serotonin and dopamine systems. Individuals who have previously participated in other stuttering-related programs of the Section and their parents are being studied. Blood samples have been collected and DNA extracted from 14 of the 23 individuals who have consented to participate. Recruitment continues for this portion of the study.